Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-tre
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ORIGINAL INVESTIGATION
Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-treated mice Sajedeh Mosaffa 1 & Hanieh Ahmadi 1 & Fatemeh Khakpai 2 & Mohaddeseh Ebrahimi-Ghiri 3 & Mohammad-Reza Zarrindast 1,4,5 Received: 6 June 2020 / Accepted: 7 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Acute restraint stress (ARS) is an experimental paradigm used for the induction of rodent models of stress-produced neuropsychiatric disorders, such as depression and anxiety. β-carbolines and serotonin (5-HT) systems are involved in the modulation of depression and anxiety behaviors. Objective This study was designed to examine the effects of intracerebroventricular (i.c.v.) injection of cinanserin (5-HT2 receptor antagonist) on harmaline-induced responses on depression- and anxiety-like behaviors in the ARS mice. Methods For i.c.v. infusion, guide cannula was surgically implanted in the left lateral ventricle of mice. The ARS model was conducted via movement restraint at a period of 4 h. Depression- and anxiety-related behaviors were evaluated by forced swim test (FST) and elevated plus maze (EPM), respectively. Results The results displayed that the ARS mice showed depressive- and anxiety-like responses. I.p. administration of different doses of harmaline (0.31, 0.625 and 1.25 mg/kg) or i.c.v. microinjection of cinanserin (1, 2.5, and 5 μg/mouse) blocked depression- and anxiogenic-like behaviors in the ARS mice. Furthermore, co-administration of harmaline (1.25 mg/kg; i.p.) and cinanserin (5 μg/mouse; i.c.v.) prevented the depression- and anxiogenic-like effects in the ARS mice. We found a synergistic antidepressant- and anxiolytic-like effects of harmaline and cinanserin in the ARS mice. Conclusions These results propose an interaction between harmaline and cinanserin to prevent depressive- and anxiogenic-like behaviors in the ARS mice. Keywords Acute restraint stress (ARS) . Harmaline . Cinanserin . Depression . Anxiety
Introduction β-Carboline alkaloids are a class of alkaloids that have prompted substantial investigation interest (Pfau and Skog * Mohammad-Reza Zarrindast [email protected] 1
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O.Box 13145-784, Tehran, Iran
2
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
3
Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran
4
Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
5
Department of Neuroendocrinology, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2004). In nature, β-carbolines are found in some of the plants, including Banisteriopsis caapi (Malpighiaceae) and Peganum harmala L. (Zygophyllaceae) (Callaway et al. 2005). The probable use of Peganum harmala in modern phyto-indole entheogen preparations is rela
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